Distribution of Minimum Inhibitory Concentrations and Resistance-associated Gene Mutations in Multidrug-resistant Mycobacterium tuberculosis Strains from Southern Türkiye: Insights on Bedaquiline, Delamanid, and Linezolid

Abstract

AIM: This study aimed to determine the Minimum Inhibitory Concentrations (MICs) of Bedaquiline (BDQ), Delamanid (DEL), and Linezolid (LZD), and gene mutations associated with drug resistance in multidrug-resistant (MDR) and susceptible Mycobacterium tuberculosis (MTB) strains isolated from clinical samples at the Cukurova University, Adana Regional Tuberculosis Laboratory. BACKGROUND: BDQ, DEL, and LZD are modern drugs used in the treatment of tuberculosis (TB), particularly for MDR and extensively drug-resistant (XDR) TB. Mutations in the atpE, Rv0678, fbiA, ddn,rrl, and rplC genes, significantly influence drug susceptibility and resistance patterns. Genetic characterization is essential for optimizing treatment strategies and managing drug-resistant TB effectively. METHODS: MICs and gene mutations were evaluated for BDQ, DEL, and LZD. Sequencing was performed for atpE and Rv0678 genes (BDQ), fbiA and ddn genes (DEL), and rrl, and rplC genes (LZD). MICs were measured using the MGIT960/ EpiCenter system, and sequences from 71 MTB strains were compared to the H37Rv reference. RESULTS: MICs for BDQ, DEL, and LZD ranged from ≤0.025 to 6.4 mg/L, 0.005 to 0.32 mg/L, and 0.125 to 2 mg/L, respectively. Among 71 isolates, nine MDR-TB strains (12.7%) had atpE gene mutations. No Rv0678 mutations were detected in either susceptible (n=30) or MDR-TB isolates (n=41). A single DEL-sensitive isolate had a ddn mutation. The fbiA, rplC and rrl genes were free of mutations. CONCLUSIONS: No genetic variants associated with resistance to BDQ, DEL, or LZD were identified. Further investigation is needed to better understand the genetic basis and mechanisms of resistance.

Keywords

• Delamanid
• Bedaquiline
• Linezolid